Correlation Between Drug-Induced Blood Pressure Elevation and Long-Term Prognosis of Tumor Patients Treated With Small Molecule Tyrosine Kinase Inhibitors Targeted to the Vascular Endothelial Growth Factor Pathway: A Meta-analysis

Abstract OBJECTIVE To evaluate whether blood pressure elevation induced by small molecule tyrosine kinase inhibitors (TKIs) targeted to the vascular endothelial growth factor pathway in the treatment of solid tumors is correlated with the anti-tumor efficacy and long-term prognosis. METHODS A systematic review with a meta-analysis was conducted using Cochrane Collaboration methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Grading of Recommendations Assessment, Development, and Evaluation guidelines. Observational, retrospective, or prospective randomized controlled studies were included if they evaluated the correlation between TKIs-induced blood pressure elevation and prognosis of patients, with at least one of the following indicators: objective response rate (ORR), progression-free survival (PFS), or overall survival (OS). Data were extracted and all studies were assessed for quality according to the Newcastle-Ottawa Scale. The primary outcome of this study was OS, while the secondary outcomes were PFS and ORR. RESULTS A total of 58 studies were considered eligible, with 10,020 patients included. TKIs-induced blood pressure elevation was significantly correlated with longer OS [the hazards ratio (HR) was 0.54 (95% confidence interval [CI] 0.49–0.61, P < 0.001) for death in patients with elevated blood pressure compared with those without], and PFS [HR was 0.55 (95% CI 0.48–0.63, P < 0.001) for disease progression in patients with elevated blood pressure compared with those without], as well as better ORR (RR = 1.86, 95% CI 1.43–2.41, P < 0.001). The subgroup analyses by intervention drugs and tumor types had similar results. CONCLUSIONS TKIs-induced blood pressure elevation is significantly correlated with better prognosis of tumor patients, thereby it may be one of the biological markers of TKI treatment. However, due to the considerable heterogeneity among the included studies in this article, caution should be exercised in interpreting this conclusion.